Bacteria are organisms that are equipped to
reproduce themselves; antibiotics attack that
machinery. But a virus is a parasite: It invades
a host cell and co-opts the cell’s own machinery
to make copies of itself—thousands of
copies at once, which means thousands
of chances to mutate and develop drug
resistance. A drug that disables a
part of the human cell that helps the virus reproduce,
though, could stop it with little risk of resistance.
“And if you can identify a host function that HIV, fl u,
and Ebola all require, you can have one drug that is
active against all three—a broad-spectrum
antiviral,” says Michael Kurilla of the National
In sti tute of Allergy and Infectious Diseases (NIAID).

The key is finding the right target—a gene, and
the protein it encodes, that the human cell doesn’t
need but the virus does. Human DNA contains
more than 20,000 genes, but in any given cell at
any given time, many are dormant; some, for
instance, are only switched on during embryonic
development. With the human genome now fully
decoded, investigators can search for targets
systematically by disabling individual genes in
many cells and seeing what happens. Zirus, a
company in Buford, Georgia, uses a three-step
process (see opening illustration); it begins by
infecting cells with a harmless retrovirus, which
splices itself randomly into human DNA, knocking
out any gene it interrupts. Other groups are
disabling selected genes with matching bits of
RNA. If the cell survives without a particular gene
and is now resistant to infection, that gene-protein
combo is a promising target for a drug.

The first such drug, Pfizer’s Maraviroc, is already
being used to treat HIV infections; it blocks a
cell-surface protein that acts as a receptor for the
virus. San Diego–based NexBio has recently begun
clinical trials of a compound called Fludase that
inactivates the receptors through which both swine
flu and seasonal flu enter respiratory cells. NIAID
is vigorously supporting such research. “Over the
next 20 to 30 years there will be a paradigm shift
in the way we approach infectious diseases,”
Kurilla says. “I think this will be emblematic of
21st-century medicine.” —Josie Glausiusz